Parkinson's disease is a progressive degenerative disease of the central nervous system. Although the primary cause of Parkinson's disease is not known, it is characterized by the degeneration of dopaminergic neurons of the substantia nigra. The substantia nigra is located in the midbrain and is involved in controlling voluntary movements. The degeneration of neurons causes a shortage of dopamine in the brain, which is believed to cause the observable symptoms of the disease. These symptoms include paucity of movement and rigidity, resting tremor, bradykinesia, and poor balance.
There are a variety of therapeutic treatments available for Parkinson's disease. The best known is levodopa, a dopamine precursor; however, treatment with levodopa can cause serious side-effects, especially over a long term. One such complication of long-term treatment with levodopa is the development of rapid fluctuations in clinical state, where a patient switches suddenly between mobility and immobility for periods ranging from a few minutes to a few hours. This phenomenon is known as the “on-off effect”, the “on” state characterized by the levodopa benefit of early normal motor functioning and the “off” state characterized by akinesia—abrupt loss of mobility, e.g, where a patient may suddenly stop while walking. Approximately half of patients on levodopa therapy will develop such on-off effects after several years of therapy.
While apomorphine hydrochloride has proved effective in treating “off” episodes in patients with Parkinson's disease, a common and serious side effect of administering apomorphine hydrochloride by subcutaneous injection is the development of subcutaneous nodules at the injection site, which can become infected, necessitating treatment or surgical involvement. A majority of people on infused apomorphine develop nodules, and a new nodule may form every time the infusion needle is re-sited, which may happen on a daily basis. Such nodules may be painful, limit available infusion sites and interfere with absorption. Further, unstable compositions, e.g., having precipitate of apomorphine or other agents, may be the cause, or exacerbate, such nodule side effects. Thus, there is a need for new, stable formulations of apomorphine which are safe and effective for administration to patients.